StemSynergy Therapeutics Inc. (SSTI) is a biopharmaceutical company focused on the discovery, development, and commercialization of drugs that target pathways fundamental to stem cells and cancer stem cells. The World Health Organization estimates that over 12 million cases of cancer were diagnosed in 2007 and that nearly 8 million cancer patients will die of their disease. Colorectal cancer (CRC) represents the third most common cause of death due to cancer with 610,000 deaths. Activating mutations in the Wnt signaling pathway are the earliest events in the genesis of CRC, and, remarkably, are present in over 90% of all cases. There is an urgent need for inhibitors of the Wnt pathway for the treatment of colorectal cancer and other Wnt- driven cancers. Currently, there are no FDA-approved drugs or drugs in late-stage clinical trials that target this pathway. SSTI has developed a powerful biochemical screen to identify Wnt inhibitors utilizing two independent readouts of the Wnt pathway. By assessing the stability of two Wnt pathway proteins, 2-catenin and Axin in a high- throughput screen, SSTI has identified small molecules that regulate Wnt signaling via activation of Casein Kinase 1a. Using a novel approach to lead optimization, SSTI has developed a new series of lead compounds that have more drug-like properties. Our successful Phase I SBIR project demonstrated that these compounds potently inhibit Wnt signaling, decrease the viability of a variety of human CRC cell lines, have good ADMET properties, and show in vivo efficacy. Additionally, SSTI was able to develop a secondary (backup series) using medicinal chemistry. Both classes of small molecules represent new chemical entities and our Phase II application outlines the next logical steps in their development by optimizing metabolism, demonstrating efficacy and performing safety studies in rodent and non-rodent. Our overall goal of this Phase II project is to demonstrate all of the necessary properties for IND submission according to the FDA guidance (ICH S9) for clinical trials of advanced colorectal cancer. Because there are no drugs on the market that target the Wnt pathway, SSTI has the potential to improve and prolong the lives of millions of cancer patients worldwide. In summary, SSTI has the opportunity to bring to the market the first generation of Wnt inhibitors and capture a significant share of the global market for cancer drugs. PUBLIC HEALTH RELEVANCE: Colorectal cancer is responsible for 1.2 million cases and 610,000 deaths each year. The Wnt pathway is a major growth pathway that plays a critical role in >90% of all cases and there are currently no inhibitors in the clinic. We intend to develop our lead compound Wnt pathway inhibitors through pre-clinical and clinical trials for a treatment of colorectal cancer.